Dialysis is the indicated treatment for patients with renal insufficiency. The removal of waste substances and excess of fluid from the blood is effected by transfer to an external fluid or by replacement of plasma liquid with an external fluid. Various dialysis techniques with associated dialysis fluids may be differentiated. Which dialysis technique to use, depends on the type of patient.
In the case of patients suffering from chronic renal insufficiency, the patient receives dialysis therapy 3-5 hours, about three times per week. The dialysis therapy is usually performed at a dialysis center, although home dialysis is also possible. When home dialysis is performed the patient is free to perform dialysis more frequently and also in a more gentle treatment with longer duration, i.e. 4-8 hours per treatment and 5-7 treatments per week. The dose and treatment duration may be adjusted to each patient's demands and needs.
In the case of patients suffering from acute renal insufficiency, a continuous treatment throughout the entire day, and in some cases for several weeks, a continuous renal replacement therapy (CRRT), is the indicated treatment.
Continuous renal replacement therapy (CRRT) can also be used in treatment of chronic renal insufficiency by using a wearable artificial kidney system. Such a system is for example disclosed in US 2008/058696.
In a dialysis treatment a portion of the patient's blood stream is lead into an extracorporeal blood circuit comprising a semipermeable membrane in which the removal of waste substances is performed and then the cleansed blood is lead back to the patient. The semipermeable membrane has a blood side and a dialysate side.
When the removal of waste substances is effected by transfer to an external fluid, the waste substances and excess fluid are transferred by diffusion through the semipermeable membrane wall into a dialysis fluid flowing on the dialysate side of the semipermeable membrane. Simultaneously as the waste substances are transferred from the blood, through the semipermeable membrane wall and into the dialysis fluid, solutes and nutrients may diffuse in the opposite direction from the dialysis fluid, through the semipermeable membrane and into the blood. This technique is called hemodialysis.
When the removal of waste substances is made by replacement of plasma liquid with an external fluid, a portion of the plasma liquid is removed from the blood by means of convective flow through the semipermeable membrane, and an external fluid (also called an infusion fluid, a replacement fluid or a substitution fluid) is added to the blood stream. This technique is called hemofiltration.
Finally the removal of waste substances may also be made by a combination of hemodialysis and hemofiltration, thus the removal of waste substances is provided by a combination of diffusion and convection through the semipermeable membrane, and the solutes and nutrients are added both by infusion in the blood stream and by diffusion from the dialysis fluid through the semipermeable membrane and into the blood. This technique is called hemodiafiltration.
Common for all the above disclosed techniques is that the blood is withdrawn from the patient continuously into an extracorporeal blood circuit, in which the removal takes place, and the “cleansed” blood is returned to the patient. When blood is removed from its normal environment within the blood vessels, the blood coagulation cascade is initiated, and in order not to clog the extracorporeal blood circuit with the coagulating blood, means for anticoagulation have to be provided.
The fluids used during the dialysis treatment, thus the dialysis fluid, the infusion fluid (also named replacement fluid or substitution fluid), have been given the comprehensive term “treatment fluids” in the following.
The treatment fluids used in all the above dialysis techniques contain mainly electrolytes like sodium, magnesium, calcium, potassium, an acid/base buffer system and optionally glucose or a glucose-like compound. All the components in the treatment fluids are selected to control the levels of electrolytes and the acid-base equilibrium within the blood.
The treatment fluids are today often prepared from different types of concentrates. It may be liquid concentrates of different degree of concentration, where the acid/electrolyte part is separated from the buffer part before use.
The treatment fluids may be prepared from concentrated volumes of 0.5-8 L in bags for bedside use, or prepared from volumes of 5-20 L in canisters, which still are for bedside use. The treatment fluids may also be prepared from concentrates in central tanks in volumes of 300-1000 L.
The concentrates may also be provided as dry powder concentrate, to be dissolved and diluted into the determined concentrations.
When using bicarbonate as a buffer component in the treatment fluids, bicarbonate may also be provided as a dry concentrate for on-line-preparation of saturated bicarbonate containing concentrate. The saturated bicarbonate containing concentrate is thereafter mixed with an acid/electrolyte concentrate and further diluted with purified water to produce the on-line prepared treatment fluid.
The treatment fluids may also be provided in bags. In some cases the treatment fluids are provided in multi-compartment bags, in which the acid/electrolyte part is contained within one compartment, and the buffer part is contained in another compartment, and where the two parts are mixed right before use in a way to maintain sterility of the treatment fluid to provide a ready-for-use treatment fluid. Also, the treatment fluid may be provided in single compartment bags.
Patients in need of dialysis are often hyperphosphatemic when starting the dialysis treatment. However, during the dialysis treatment phosphate is removed from the patient and if no counteraction is taken the patients may become hypophosphatemic. In order to counteract this loss of phosphate during the treatment, phosphate containing dialysis fluids have been developed and introduced on the market. As a consequence the variability of patient serum phosphate levels as well as the incidences of hypophosphatemia has been significantly reduced.
Anticoagulation for dialysis patients are today often provided by heparin injections or by regional anticoagulation using citrate infusion into the extracorporeal blood.
Citrate containing fluids are previously known. A citrate containing replacement fluid is described in WO 2007/059145 A2.
In US2008/0015487A1 is a replacement fluid comprising citrate and phosphate described. However, due to the low content of citrate this fluid is considered unsuitable as anticoagulation fluid.
The use of citrate as an anticoagulant for dialysis patients is increasing. A fluid containing sodium citrate and/or citric acid is then infused close to the blood access where the blood exits the patient and enters into the extracorporeal blood circuit. Citrate acts as an anticoagulant by lowering the ionized calcium concentration within the plasma, through calcium citrate complex formation. Ionized calcium is essential for the blood coagulation cascade. If the ionized calcium level is lowered well below 0.5 mM, the blood coagulation cascade is prevented. Citrate that exists in the blood is rapidly metabolized, and theoretically three bicarbonate ions are formed from each citrate ion. As the citrate concentration is lowered in the metabolism, citrate complex bound calcium is released and returns to ionized calcium.
Today citrate is delivered to the clinics in sterilized pre-prepared anticoagulation fluid bags with citrate concentrations between 10-400 mM. Depending on the citrate concentration of the pre-prepared anticoagulation fluid, many liters of this citrate may be infused into the patient in order to provide proper anticoagulation during the treatment.
However, the use of many liters of the pre-prepared anticoagulation fluid often leads to situations when too much of the desired treatment dose is supplied by the anticoagulation fluid leaving too little room for using other treatment fluids, such as dialysis fluid and/or added infusion fluid (also named replacement fluid or substitution fluid). Thus, this limits the possibility of balancing the correct amount of phosphate within the blood in order to compensate the phosphate removal in the semipermeable membrane. One way of rendering this problem is to include the phosphate in the anticoagulation fluid.